Thrombomodulin, also known as BDCA-3, is a glycosylated transmembrane protein present on the surface of vascular endothelial cells. Thrombomodulin is a high-affinity receptor for thrombin, a key protein in the coagulation cascade. Formation of the thrombomodulin-thrombin complex blocks the thrombin dependent conversion of fibrinogen to fibrin and also catalyzes the activation of protein C. Active protein C is able to proteolytically inactivate enhancers of the coagulation cascade. Thrombomodulin’s dual ability to directly block thrombin function and to activate a negative regulator of coagulation makes it essential component of the anticoagulation system. Thrombomodulin is known for its role in anticoagulation but has recently been shown to have important functions in inflammation as well. The extracellular N-terminus of thrombomodulin consists of two domains; a lectin-like domain and an EGF-repeat domain. The EGF-repeat domain is responsible for thrombin binding however the lectin-like domain plays no role in anticoagulation. Rather this domain is important for cell adhesion and inflammation. This lectin-like domain suppresses inflammation by binding to and inactivating pro-inflammatory molecules. One of these binding partners is high mobility group box 1 (HMGB1) protein, a pro-inflammatory protein released from necrotic cells or secreted by inflammatory cells. The other characterized binding partner is the Lewis Y antigen found in lipopolysaccharide (LPS) of gram-negative bacteria. Thrombomodulin binding of these targets blocks the activation of MAPK and NF-kB pathways and inhibits inflammation (1).
Thrombomodulin antibodies are effective tools to study these essential functions in coagulation and inflammation. In addition to immunohistochemistry and immunoblotting thrombomodulin antibodies can themselves be used as reagents in experiments to manipulate biological systems. A recent study from the University of Minnesota elucidated the mechanism of vaso-occlusion in a mouse model of sickle-cell anemia (2). The researchers used thrombomodulin antibodies along with a panel of others to target and block cell surface adhesion proteins present on endothelial cells. This study identified P-selectin, von Willebrand factor, and E-selectin among others as important factors contributing to vaso-occlusion. Similarly, Greineder et al. from the University of Pennsylvania used a polyclonal thrombomodulin antibody to test their therapeutic fusion protein consisting of an antibody targeted thrombomodulin domain (3). This endothelial targeted fusion was successful at activating protein C and this result was specific as treatment with thrombomodulin antibodies blocked the effect.
Novus Biologicals offers Thrombomodulin reagents for your research needs including: